Wednesday, September 26, 2012

Dr. James G. Pfaus, a Professor of Psychology at Concordia University in Montreal, recently wrote a post in defense of Naomi Wolf's neuroscience acumen. This is understandable, as he was one of her main sources of scientific information about the "brain-vagina connection" in Vagina: A New Biography. Wolf, as you know, has been under fire for her simplistic and gendered treatment of cortisol and dopamine, as if these chemicals have highly specific effects on adult feminist women (and their vaginas), but no one else.1

Pfaus's general reply to that line of criticism is that we should let Wolf have poetic license with her storytelling:

Is Wolf right in regarding dopamine as the "ultimate feminist
neurochemical"? It is certainly unlikely that sea slugs and nematode
worms are feminists. But can't we allow an accomplished writer and
social critic a little poetic leeway to make a point?

Wolf's search took her, among other places, to my laboratory. We had
been doing research on the role of clitoral and vaginocervical
stimulation in the sex and reproductive lives of female rats, work that
has been published in high-quality peer-reviewed scientific journals.
This work revealed that such stimulation, when applied in the right way,
induces a state of sexual reward that conditions place and partner
preferences (the latter of which was unexpected in an allegedly
promiscuous and polygamous species). Taken together with previous work
from my laboratory showing the profound role of dopamine and opioid
neurotransmitters in both male and female sexual behavior, and in the
context of a more general scientific literature in animals and humans
showing that blockade of those transmitters induces varying degrees of
an "anhedonic" state akin to depression in which reward does not occur
and animals do not focus their attention toward it anymore, it became
clear to Wolf that these neurochemicals were important parts of the
sexual desire and pleasure systems of the brain.

Pfaus is a prolific scientist whose work ranges from basic animal models and translational research to establishing definitions for human sexual disorders. Now that more of Vagina is online at Amazon, I see that Wolf relied heavily on his research (he's mentioned 26 times), and that she cited many original sources from the scientific literature (albeit not always correctly).2

Which brings us to animal models for what we typically regard as profoundly human states: longing, angst, futility. Or Desire, Dread, and Despair. The words don't easily
lend themselves to rodent analogues, because they remind us of an unrequited crush or an existential crisis. Certainly, rats don't write love letters or read Kierkegaard or appreciate Expressionist art. Dark Night of the Soul (the original poem) was written by a Roman Catholic mystic to describe the painful journey of a bride (soul) in search of her groom (God). Today it indicates a spiritual crisis, a state of profound aloneness, a crushing existential despair.

The animal models of these states are more mundane and less abstract, yet important for potentially explaining the neural mechanisms underlying human suffering: addiction, anxiety, and depression. But are they really adequate stand-ins for the human condition? Of course not. My purpose here isn't to critique animal research, but rather to consider actual behaviors and how they map onto the terminology used to describe them.

Desire

For our present purposes, desire is defined in terms of sexual behavior. Specifically, sexual desire includes the anticipation of and motivation for participation in sexual activity. In rats, "Desire is inferred by certain measures, such as solicitations, rates of pacing (in which female rats control the initiation and rate of copulatory contact with male rats), and the strength of operant behavior aimed at acquiring sex partners" (Pfaus, 2006).

Modified from FIG. 1 (Pfaus, 2006). Incentive sequences for human and rat sexual behavior (modified from Pfaus et al., 1999). The behavioral stream moves from left to right, through appetitive, precopulatory, and consummatory phases of behavior. This conforms to the movement of animals from distal to proximal to interactive with respect to the sexual incentive.

In Fig. 1 we can see that female rat Excitement (grooming, investigation, motor activation) maps onto female human Sexual Desire (fantasy, excitement). Sexual fantasy is decidedly absent from the repertoire of rats, so conditioning and preference paradigms serve that purpose. Meanwhile, female rats show subsequent stages of defensiveness and lordosis, while female humans get to have orgasms. Fig. 2 in the Pfaus paper shows four panels of appetitive and consummatory measures of copulation in a pair of rats. Solicitation, investigation, running away, pursuit, lordosis, and mounting took all of 4 seconds. This goes on for several bouts until the male ejaculates. Wolf's "Goddess Array" is nowhere to be found.

Indeed, one of the places where Wolf went most astray in Vagina was in her wild extrapolations from the neurobiology of Pfaus's rats to the "Goddess Array" and what women need sexually: candles, flowers, music, or
some other romantic gesture ("A whole set of words, actions, and
gestures that women cannot do without"). Even if this were universally
true, it obviously involves the kind of cognitive capacity well beyond
rats.

Nonetheless, a major goal of the animal model is to serve as a preclinical testing ground for perceived sexual dysfunction in humans, including the categories of Hypoactive Sexual Desire Disorder (HSDD) and Female Sexual Arousal Disorders, which are distinct (and yet overlapping, according to some). In his accurately (but inelegantly) titled review Of rats and women: preclinical insights into the nature of female sexual desire, Pfaus (2006) stated:

Many clinicians and motivational theorists alike view desire as distinct from arousal in both animals and humans. This is apparent in the DSM’s categorization of arousal disorders distinct from desire disorders, a distinction that generally reflects blood flow to the genitals and erectile tissues versus a ‘psychological’ sexual interest in which individuals ‘want’ or ‘crave’ sex (Robinson & Berridge, 1993).

The neurochemical distinctions between ‘wanting’ [incentive salience] and ‘liking’ (in sum, dopamine vs. opioids) have been extensively studied by Kent Berridge and colleagues as applied to addiction. However, simplistic notions that low dopamine = low libido and depression in women (Wolf, p. 57) are not clearly supported by the literature.3

It's also important to note that HSDD is a controversial clinical diagnosis, one given to women who have a low (or
nonexistent) libido and are distressed about it. However, desire is highly subjective, and what might be distressing to one woman is of no concern to another. Examining the causes of diminished sexual desire is critical, and these can include non-sexual health problems, menopause,4 a house full of kids, relationship issues, and having a crappy lover. Dr. Petra Boynton has
written extensively about the problematic aspects of the HSDD diagnosis and the screening tools used to assess it, as well as the medicalization of sexuality for pharmaceutical marketing purposes.5

In general, you know that something is nosologically amiss when a review article claims that "Over 50% of women are believed to be affected by female sexual dysfunction" (Woodis et al., 2012). Which brings us to a state of dread...

Dread

Desire can turn to dread very quickly in human relationships. This is also true in the rat mesolimbic dopamine system. Recent studies (e.g., Faure et al., 2008) have suggested that "desire" and "dread" reside in close proximity in the nucleus accumbens (NAc). Appetitive and aversive motivations can be elicited by manipulations of
glutamate or GABA systems located only millimeters apart in the NAc.(Richard & Berridge, 2011):

NAc and dopamine-related circuits are best known for roles in appetitive motivation, but are also implicated in some forms of aversive motivation related to fear, stress, disgust, and pain. Within medial shell of NAc, neuroanatomical coding plays an important role in determining appetitive versus fearful valence
of intense motivations generated by glutamate disruptions.

The measured behaviors in these experiments are actually called "desire" and "dread" (Richard & Berridge, 2011; 2012). Desire is the time spent eating food chow pellets, and dread (fear) is the time spent kicking up crushed corn cob bedding at threatening stimuli, a behavior known as defensive treading. The figure below shows an anterior-posterior gradient for desire and dread in the NAc medial shell. The glutamate AMPA receptor anatgonist DNQX was microinjected alone or in combination with D1/D2 dopamine antagonists into subregions of the NAc. Glutamate disruption in the anterior region induced eating, but glutamate disruption in the posterior region induced defensive treading. Both effects were reversed by dopamine antagonists, suggesting that the behaviors were mediated by dopamine.

In real life, it seems that such anatomically discrete manipulations of NAc would not be the norm. This might suggest that a mixed feeling of desire and dread is more typical: you want to eat that donut bacon cheeseburger but fear the extra pounds (or a heart attack). Or you desire the sultry stranger who showed up in your shower but dread the consequences of unravelling the mystery (or at least you do in a David Lynch movie).

Fortunately, the NAc is sensitive to emotional context, so the "desire-dread" map can show plastic changes according to the current environment (Reynolds & Berridge, 2008). Under standard conditions (neither very safe nor very stressful), there's a yellow zone of ambiguity in the middle.

Ambivalent states are more computationally intensive for the Bayesian brain, and preferences for novel, surprising, and even inexplicable experiences (such as Mulholland Drive) present a challenge for Bayesian theorists and their "free energy principle" (see Free-energy minimization and the dark-room problem), which seeks to reduce uncertainty. Motivations aren't always clear-cut, even in rat NAc. Fortunately, the NAc doesn't exist in isolation, and top-down influences from medial prefrontal cortex can bias or suppress intense motivations (Richard & Berridge, 2012).

For other realms of dread, there's a very large literature on fear conditioning, as most of you know.

In her opus on the powers of horror, Kristeva (1982) delineates a realm of preverbal experience permeated by affects of meaninglessness, dread, and horror. Her constructs of abject states and self-abjection are complex amalgams of identity, attachment disorganization, affect, and enactment. ... Whereas the masochist suffers to gain nurture, the abject self suffers in the certain knowledge that he/she is beyond help.
... In the grip of abject feelings, one feels unworthy, unlovable, and in utter despair about the situation ever changing.

That terrifying sense of existential dread and aloneness is not exactly captured by animal models of behavioral despair. There's a gaping chasm between Kristeva's abject states and depressive-like behaviors in mice exposed to chronic stress. The animals may give up in the forced swim test, but they're not filled with self-loathing in the face of their inadequacy.

I tried to write in greater detail about this topic in 2009 but gave up. In despair of ever finishing. The post was titled Is There a Valid Animal Model of Depression? but the literature was too large to sufficiently summarize in a single post. In fact, you might need an entire blog that touches on these issues, so head right over to Functional Neurogenesis to read the posts tagged anxiety/depression. Oh, and you can take a look at my early attempt from six years ago: Sad Cingulate on 60 Minutes and in Rats.

I don't care if you're sad
I don't care if you're heart is breaking
You soothe me and you turn me on
Speed and sleep

2 However, the sources she used were misstated at times... as in this gift that just keeps giving (Vagina, p. 290):

Specific scents have been found to boost vaginal blood engorgement: cucumbers and Good & Plenty candies both are at the top of the vaginal-engorgement-activating scents, according to one study (and both are phallic in shape).

"Honey, I'm tired of the cucumber. Can we use the Good & Plenty tonight?" But seriously, she cited Zhou and Chen (2008) for this, which is incorrect. Who fact checked this book??

3 For example, in a group of individuals with Parkinson's
disease (all of whom were under dopaminergic treatment),
Celikel et al. (2008)
found that: "Female patients had reduced sexual drive and they were
less satisfied with orgasm, while male patients had easier orgasms than
did the controls." Wolf cited a study that reportedly found "a link
between well-functioning dopamine (and norepinephrine) systems and
strong female sexual response" (p. 58), but the authors themselves did not observe
that: "Our prediction that women with HSDD and FSAD would show
substantially lower DA and NE responses to sexual stimuli was not
supported" (Meston & McCall, 2005). Finally, the dopamine and norepinephrine reuptake inhibitor bupropion has been shown to improve sexual functioning in some studies of depressed humans, but it had no effect on sexual motivation and copulatory behavior in female rats (López et al., 2007). Also see a detailed post by David Dobbs, in response to Dr. Pfaus.

4 Naomi Wolf is about to turn 50, and I predict she's already working on a sequel to Vagina: A New Biography -- one that involves menopause.

Friday, September 14, 2012

Are you one of the few Anglophones who haven't yet heard about the frightening new fields of neuromarketing and neuroeconomics? Or that pop neuroscience is popular? Well thank god we have Steven Poole to set us straight!

An intellectual pestilence is upon us. Shop shelves groan with books purporting to explain, through snazzy brain-imaging studies, not only how thoughts and emotions function, but how politics and religion work, and what the correct answers are to age-old philosophical controversies. The dazzling real achievements of brain research are routinely pressed into service for questions they were never designed to answer. This is the plague of neuroscientism – aka neurobabble, neurobollocks, or neurotrash – and it’s everywhere.

It may be "everywhere" but it's been around for a while. But you wouldn't guess from reading Poole, who acts as if he's discovered this infectious plague all by himself. He hasn't noticed that many others before him have closely examined and criticized the misuse of brain science to sell self-help books or to advance an academic career. Even his neurowords are old, invented or popularized by other people. Raymond Tallis, for instance, is known for neurotrash and neuroscientism. But even Tallis didn't coin these words.1

Poole hasn't done his homework, which is unfortunate for someone who uses terms like "intellectual pestilence" as a casual insult. Perhaps he should know more about the fields he ridicules:

Happily, a new branch of the neuroscienceexplains everything genre may be created at any time by the simple expedient of adding the prefix “neuro” to whatever you are talking about. Thus, “neuroeconomics” is the latest in a long line of rhetorical attempts to sell the dismal science as a hard one; “molecular gastronomy” has now been trumped in the scientised gluttony stakes by “neurogastronomy”; students of Republican and Democratic brains are doing “neuropolitics”; literature academics practise “neurocriticism”. There is “neurotheology”, “neuromagic” (according to Sleights of Mind, an amusing book about how conjurors exploit perceptual bias) and even “neuromarketing”.

...gets “exasperated” by much popular coverage of neuroimaging research, which assumes that “activity in a brain region is the answer to some profound question about psychological processes. This is very hard to justify given how little we currently know about what different regions of the brain actually do.” Too often, he tells me in an email correspondence, a popular writer will “opt for some sort of neuro-flapdoodle in which a highly simplistic and questionable point is accompanied by a suitably grand-sounding neural term and thus acquires a weightiness that it really doesn’t deserve. In my view, this is no different to some mountebank selling quacksalve by talking about the physics of water molecules’ memories, or a beautician talking about action liposomes.”

But these important points get buried in the bile inflicted on Jonah Lehrer and Malcolm Gladwell. Haven't they been beaten to death already? And it's not at all clear why he would go after distinguished cognitive scientist Dr. Art Markman and lump him in with the highly discredited agenda of neurolinguistic programming:

Mastering one’s own brain is also the key to survival in a dog-eat-dog corporate world, as promised by the cognitive scientist Art Markman’s Smart Thinking: How to Think Big, Innovate and Outperform Your Rivals. The field (or cult) of “neurolinguistic programming” (NLP) sells techniques not only of self-overcoming but of domination over others.

Markman's book has different subtitles in the US and the UK, but it doesn't yammer on about neuro-anything, from what I can tell (and only mentions the word "brain" 7 times).

A number of neurobloggers and journalists have been tackling shoddy neuroscience for years, whether in journal articles or books or mainstream media.3The Neurocritic has extensive coverage of books [and other claims] by Louann Brizendine and Daniel Amen, for instance, along with copious criticism of media coverage and press releases that distort and exaggerate neuroscience findings.

Along with Mind Hacks, one of the major influences on this blog was Bad Neurojournalism (later renamed the Neuro-Journalism Mill), a collection of bad neuroscience journalism from 1998-2009, compiled by a comedian at the James S. McDonnell Foundation. A few examples (all definitely worth the click):

neurogibberish: Seemingly impressive jargon used by some neuroscientists to hide lack of real findings. (E.)

neuroessentialism: the belief in, or tactic of, invoking evidence, or merely terms, from neuroscience to justify claims at the psychological level. See also neuromysticism, neurobollocks. (Tom Stafford)

Neuroeconomics is a purely academic discipline concerned with the basic mechanisms of decision-making. In contrast, Neuromarketing is a more applied field concerned with the application of brain scanning technology to the traditional goals and questions of interest of marketers, both those in academia and those in private industry. While these two disciplines are related, they are also very distinct. This is a distinction often overlooked by the popular media.

The technology is seductively easy to use, said Dr. Christopher Moore, a postdoctoral fellow at Massachusetts General Hospital in Boston who is carrying out a number of imaging studies. ''You can think of an idea, throw five friends into the scanner overnight and write up your results the next day. People don't have to think very hard about what they're doing.''

Tuesday, September 11, 2012

...the battle between reason and emotion takes center stage. A professor, who believes she has found a way of determining scientifically whether someone is in love, clashes with her department chair, a woman who thinks love and attraction are far too complex to be mapped according to the certainties of science.

The clip above highlights a hilarious event designed to determine the neural correlates of love. How does it work?

"Well, the goal is to identify the part of the brain that controls lust, and to show that it is different from the part of the brain that controls love. In order to do this we had to simulate as natural an environment as possible while still being able to measure neural activity. So I have created the Electroencephalogram Cocktail Party. An EEG Mixer!!"

Draganosky received an Alfred P. Sloan Foundation grant for The Science of Love. She spent a year researching the film, attending presentations and conducting interviews in the laboratory of Dr. Joy Hirsh at Columbia. "I actually audio-taped the interviews because I wanted to get all the scientist-speak perfectly right so that I could write accurate dialogue." We can certainly forgive the confusion of fMRI and EEG results for artistic sake (and comic effect) here. The lead character Syd seems to be modeled after Dr. Helen Fisher, even down to the combination of evolutionary anthropology with brain imaging.1

The cocktail party was unscripted, other than withholding drinking for the first 10 minutes to record a pre-drinking baseline. The partiers intermingled, chatted, ate sushi and hors d'oeuvres and drank vodka martinis or vodka and cranberry cocktails according to their personal inclinations. They also measured BACs [breath alcohol content], took photos and checked up on the automated data collection.

The goal here was not to evaluate the effectiveness of EEG Speed Dating or to explicate a lofty ScienceofLove, but instead to examine the effects of alcohol on the spectral properties, or frequency composition, of EEG in a naturalistic setting. Although the technique of "hyperscanning"3 has been used in fMRI studies, the advantages of EEG recording in this context should be obvious.4

The participants served as both subjects and experimenters:

Teams placed headsets simultaneously on groups of participants; total set up time was about a half hour. Data from each EEG headset was transmitted during the party via Bluetooth protocol to its own dedicated notebook computer. The data were time synchronized across computers by a start signal sent via local Ethernet from one computer to all other recording computers.

They measured breath alcohol contents, took photos and checked the data collection.5

Using data obtained from two prior experiments (collected from separate groups of subjects in a more typical recording environment), multivariate divergence analyses searched for the subset of variables6 that best discriminated between the EEGs of brains on alcohol vs. brains on placebo. These equations were applied to the pre- and post-alcohol EEGs of the partygoers. Although 40% of the ambulatory cocktail party data were lost due to artifacts, the remaining data showed 80% sensitivity in recognizing alcohol and 80% specificity in recognizing no-alcohol. While mandatory Wearable Wireless EEG Fashion Accessories will not be replacing breathalyzers at sobriety stops any time soon, this was certainly a fun pilot study (especially for the participants)!

Footnotes

1Recycling Alert: this paragraph contains portions of my original 2006 review of the entire 18 minute short (combined with additional information). It's only two sentences, but I need to be forthcoming in anticipation of my future blogging gigs at Wired and the New Yorker.

3The hyperscanning technique was developed by Read Montague and co-workers (Montague et al., 2002). Typically, hyperscanning involves two subjects who interact with each other while playing a "trust" game. Their brains are scanned simultaneously (in adjoining or distant magnets). Specially developed software coordinates the experiments across sites.

4You can't walk around, eat, drink, and directly interact with others while lying in a scanner.

5 Who's real and who's fictional??

6 Technical details:

The individual frequency component powers were then averaged into 3 standard bands, theta (4–7 Hz), alpha (8–13 Hz) and beta (13–18 Hz) determined in prior studies to be sensitive to alcohol's effect on the EEG. The 3 banded powers and their standard deviations constituted a total set of 6 variables for each of the 7 electrode sites.

Could a profound connection between a woman’s brain and her experience of her vagina affect her greater sense of creativity—even her consciousness? In her provocative and important new book, ... bestselling author of The Beauty Myth Naomi Wolf argues that this connection is not only real—and long-overlooked—but that it is fundamental to a woman’s sense of self.

Spurred by the experience of an unexpected medical crisis – an injured pelvic nerve that temporarily affected her own physical sensation – Wolf set out to uncover why and how the brain and vagina are really best understood as “one system.” Understanding the brain-vagina connection, she learned, is not merely a key to more transformative sex for women – it is a key to female self-actualization, and thus to female power, creativity and confidence.

This unlikely combination of pseudoscientific and mystical elements provides a little something for everyone to hate. Among neuroscientists, howlers such as "dopamine is the ultimate feminist chemical in the female brain", oxytocin "is women's emotional superpower" and the vagina is "not only coextensive with the female brain but also is part of the female soul" have been making the rounds of social media.

I almost feel sorry for Ms. Wolf because it's like shooting fish in a barrel. Dopamine is not a feminist neurotransmitter, unless snails and insects have been secretly reading Betty Friedan and listening to Bikini Kill.

Chapter 4 of Vagina is on Dopamine, Opioids, and Oxytocin. Other than the excerpt and review in the Guardian, only three pages of the chapter were available online. But here's one choice quote:

Those of us who are not scientists often forget that brain chemicals are vehicles for very profound human truths.

I thought brain chemicals were vehicles that bind to receptors and trigger signal transduction molecules. Even the most reductionistic neuroscientists among us realize we are worlds away from understanding how oxytocin might explain morality (Paul Zak notwithstanding).

But feminist biology apparently tells us that the vagina is the delivery system for profound female truths:

By the same token, a female self's experience of freedom, and its impulse to seek more freedom, and to do so from a basis of self-love -- the feminist quest and the feminist sensibility -- are all strengthened in women by preorgasmic dopamine, and by the effect of orgasm on the brain. ... So in this way, the vagina is the delivery system for the states of mind we call confidence, liberation, self-realization, and even mysticism in women.

So women who aren't having orgasms cannot be confident liberated feminists?? Sure makes you wonder about Wolf's scientific sources...

Is Wolf at fault here? Was it her responsibility to contact actual experts (or even know who they are)? I can't say who else she might have consulted, having only read a small sampling. In Chapter 2, she cited a serious 1996 paper by Meston and Gorzalka on Differential effects of sympathetic activation on sexual arousal in sexually dysfunctional and functional women. But then she says:

The autonomic nervous system prepares the way for the neural impulses that will travel from vagina, clitoris, and labia to the brain, and this fascinating system regulates a woman's responses to the relaxation and stimulation provided by "the Goddess Array," the set of behaviors a lover uses to arouse his or her partner.

The Goddess and the autonomic nervous system -- together at last or odd bedfellows? In the end (or rather, the beginning), Vagina is part autobiography, and Wolf certainly exposes herself and her orgasms, which in my mind makes her even more vulnerable to personal attacks. I'll stick to the neuroscience for now, and await the sequel.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.